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PubMed1985

Comparison of amphotericin B and N-D-ornithyl amphotericin B methyl ester in experimental cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis.

Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis in rabbits. Antifungal activity of the two polyenes in vitro was similar for the yeasts used in these experiments. N-D-ornithyl amphotericin B methyl ester gave a slightly higher concentration in serum than amphotericin B did, but both drugs had similar elimination curves, and penetration into the cerebrospinal fluid was poor for both. Despite these similarities between the two polyenes, amphotericin B was much more effective than N-D-ornithyl amphotericin B methyl ester in the treatment of cryptococcal meningitis in rabbits. For C. albicans endocarditis, both polyenes had similar cure rates, but in vitro measurement of fungicidal activity in serum did not predict treatment outcome. For C. albicans pyelonephritis, both polyenes showed efficacy; because higher doses of the less toxic methyl ester could be used, it sterilized the urinary tract more often than amphotericin B. These studies indicate that in vivo and in vitro experiments may be needed to predict the results of treatment with polyenes.

Amphotericin B↗

PubMed1992

Comparison of 5 milligrams of netilmicin per kilogram of body weight once daily versus 2 milligrams per kilogram thrice daily for treatment of gram-negative pyelonephritis in children.

The efficacy and safety of netilmicin, 5 mg/kg of body weight once daily or 2 mg/kg thrice daily for 10 days, for the treatment of gram-negative pyelonephritis in children were compared in a prospective, randomized trial. Explicit criteria were used to define the site of infection, treatment outcome, and adverse effects. Netilmicin was given to 74 children once daily and to 70 children three times daily. At 1 week posttreatment, 73 (99%) of 74 children treated with netilmicin once daily and 70 (100%) of 70 children treated with netilmicin three times daily were cured. At 4 weeks posttreatment, no relapse was detected and the rate of reinfection was essentially identical in the two treatment groups. Peak serum netilmicin concentrations were higher in patients given the once-daily regimen, whereas a higher trough level was detected in patients given the three-times-daily regimen. Nephrotoxicity, which was defined as an increase in the serum creatinine level of greater than or equal to 0.3 mg/dl over the baseline, was rare (3%) and reversible and occurred regardless of the treatment regimen. Ototoxicity, which was assessed by pure-tone audiometry (250 to 8,000 Hz) and brain stem-evoked response (6,000 Hz), occurred in 2 of 32 children who were evaluated. In these two children, who were given the once-daily regimen, wave V was not evokable monolaterally below 25 and 40 dB normal hearing level, respectively. Thus, it may be possible to treat childhood pyelonephritis with netilmicin once daily. However, this new approach needs to be confirmed in other studies.

Child↗

PubMed1999

Efficacies of high-dose fluconazole plus amphotericin B and high-dose fluconazole plus 5-fluorocytosine versus amphotericin B, fluconazole, and 5-fluorocytosine monotherapies in treatment of experimental endocarditis, endophthalmitis, and pyelonephritis due to Candida albicans.

We compared the efficacies of fluconazole (Flu), amphotericin B (AmB), and 5-fluorocytosine (5FC) monotherapies with the combination of Flu plus 5FC and Flu plus AmB in a rabbit model of Candida albicans endocarditis, endophthalmitis, and pyelonephritis. The dose of Flu used was that which resulted in an area under the concentration-time curve in rabbits equivalent to that seen in humans who receive Flu at 1,600 mg/day, the highest dose not associated with central nervous system toxicity in humans. Quantitative cultures of heart valve vegetations, the choroid-retina, vitreous humor, and kidney were conducted after 1, 5, 14, and 21 days of therapy. All untreated controls died within 6 days of infection; animals treated with 5FC monotherapy all died within 18 days. In contrast, 93% of animals in the other treatment groups appeared well and survived until they were sacrificed. At day 5, the relative decreases in CFU per gram in the vitreous humor were greater in groups that received Flu alone and in combination with 5FC or AmB than in groups receiving AmB or 5FC monotherapies (P < 0. 005) but were similar thereafter. In the choroid-retina, 5FC was the least-active drug. However, there were no differences in choroidal fungal densities between the other treatment groups. On days 5 and 14 of therapy, fungal densities in kidneys of AmB recipients were lower than those resulting from the other therapies (P < 0.001 and P < or = 0.038, respectively) and AmB-plus-Flu therapy was antagonistic; however, all therapies for fungal pyelonephritis were similar by treatment day 21. While fungal counts in cardiac valves of Flu recipients were similar to those of controls on day 5 of therapy and did not change from days 1 to 21, AmB therapy significantly decreased valvular CFUs versus Flu at days 5, 14, and 21 (P < 0.005 at each time point). 5FC plus Flu demonstrated enhanced killing in cardiac vegetations compared with Flu or 5FC as monotherapies (P < 0. 03). Similarly, the combination of AmB and Flu was more active than Flu in reducing the fungal density in cardiac vegetations (P < 0.03). However, as in the kidney, AmB plus Flu demonstrated antagonism versus AmB monotherapy in the treatment of C. albicans endocarditis (P < 0.05, P = 0.036, and P < 0.008 on days 5, 14, and 21, respectively).

Amphotericin B↗

PubMed2004

Evaluation of inflammatory and renal-injury markers in women treated with antibiotics for acute pyelonephritis caused by Escherichia coli.

The evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.

Acute Disease↗

PubMed1977

Local immune response to lipoprotein of the outer membrane of Escherichia coli in experimental pyelonephritis.

The local immune response to the lipoprotein of the outer membrane of Escherichia coli O6:K13:H1 was determined in experimental hematogenous pyelonephritis in rabbits. Local antibody was analyzed with the enzyme-linked immunosorbent assay on newly synthesized protein from kidney. Local or intrarenal antibody was detected by day 7 of infection, a few days later than serum antibody. The synthesis of antibody in immunoglobulin G class was present 6 days before the synthesis of immunoglobulin M antibody. Antibody activity to this antigen was also present in urine, and antibody could be eluted from bacteria coated with antibody. Local antibody to the lipoprotein was synthesized in equal quantities by animals infected with a heterologous species of E. coli. This antigen was not as mitogenic for splenic or kidney lymphocytes as was the O antigen. Hence, the lipoprotein of the organisms is a potent immunogen but a weak mitogen locally in pyelonephritis. This antibody response probably does not induce protection against infection, but represents a marker for presence of infection.

Animals↗

PubMed1978

Influence of iron on Corynebacterium renale-induced pyelonephritis in a rat experimental model.

Growth of Corynebacterium renale in vitro on low-iron medium (1.34 micron) was only slightly less than that on high-iron media (7.16 and 9.85 micron). However, studies on C. renale-induced pyelonephritis using the rat as an experimental model revealed that C. renale cultivated in high-iron media was capable of producing pyelonephritis, but when grown on low-iron medium, these bacteria were noninfective. This apparent avirulence of the bacteria cultivated on low levels of iron could be reversed by injecting the rats intramuscularly with ferric ammonium citrate.

Animals↗

PubMed1981

Local immune response to Escherichia coli pili in experimental pyelonephritis.

The local immune response to pili of Escherichia coli O6:K13:H1 was determined in experimental hematogenous pyelonephritis in rabbits. Pili purified from sheared cells by ammonium sulfate precipitation were found to be pure by electron microscopy and negative for lipopolysaccharide by limulus lysate assay. Antipilus antibody was detected in serum and newly synthesized protein from infected animals with enzyme-linked immunosorbent assay. Serum and local (intrarenal) antibodies were of the immunoglobulin G class, were detectable by day 20 of infection, and persisted though 250 days of infection. These data suggest that pili are present on the organism at the site of infection, since they induce the local synthesis of antipilus antibody in experimental pyelonephritis.

Animals↗

PubMed1981

Experimental retrograde pyelonephritis and cystitis induced in rabbits by a group D Streptococcus sp.: serum antibody assay by a hemagglutination test.

Experimental models of urinary tract infection caused by a group D Streptococcus sp. in rabbits are described: retrograde pyelonephritis was induced by injecting 10(9) group D streptococci into the renal pelvis and obstructing the ureter by ligature for 24 h; cystitis was induced by injecting 5.10(9) group D streptococci through a transurethral catheter. The animals were observed for 3 months. Microbiological data from the urine and from the renal parenchyma were well correlated in 12 of 14 animals. A hemagglutination test for titration of serum antibodies in these infected rabbits is described. Before the beginning of experimentation, hemagglutination titers for all animals were below 160. During experimentation, titers for rabbits with cystitis were always below 640; in those with pyelonephritis, the highest titer was much greater than 640. These results show a positive correlation between serum antibody levels and the localization of urinary tract infection.

Animals↗

PubMed1981

Experimental Candida albicans, Staphylococcus aureus, and Streptococcus faecalis pyelonephritis in diabetic rats.

Pyelonephritis was studied after an intravenous injection of Candida albicans, Staphylococcus aureus, or enterococcus in alloxan-diabetic rats and in water-diuresing or non-diuresing nondiabetic rats. The renal microbial populations of C. albicans or S. aureus were found to be greater than 10(5) colony-forming units per g for up to 42 days in diabetic rats, whereas the kidneys tended to become sterile in nondiabetic rats. No significant difference was found in the course of enterococcal pyelonephritis in diabetic versus control rats. The difference in the 50% infective dose for each microorganism between diabetic and control rats was less than or equal to log10. Neither duration of diabetes nor weight loss contributed to the greater and more sustained renal populations of C. albicans and S. aureus in diabetic rats. The inflammatory reaction in kidneys infected with S. aureus or C. albicans was greater in diabetic rats. Fungus balls associated with ureteral obstruction and gross multiple renal abscesses occurred in diabetic, but not in nondiabetic, rats infected with Candida. Growth of C. albicans and S. aureus in vitro in urine from diabetic rats was significantly greater than it was in urine from control rats. Addition of water or glucose to the urine of non-diuresing, nondiabetic rats significantly increased in vitro growth of S. aureus and C. albicans. These studies demonstrate greater severity of infection in the diabetic kidney due to S. aureus and C. albicans, which can be partially explained by decreased inhibitory activity of urine for these organisms in diabetic rats.

Animals↗

PubMed1982

Serological response to Escherichia coli pili in pyelonephritis.

The serological response to Escherichia coli pili was studied in 4 adult male patients with pyelonephritis and in 11 uninfected controls. Antibody to the specific pilus antigen of the infecting strain of each patient was measured with indirect immune electron microscopy. Antibody to a cross-reacting antigen of the type 1 pili of heterologous E. coli 346 was quantitated with an enzyme-linked immunosorbent assay. Few antipilus antibodies were found in the serum of control patients with either technique. All pyelonephrine patients developed an increase in specific antipilus antibodies belonging to the immunoglobulins classes G, A, and M. Antibodies to the cross-reacting type 1 pilus antigen were found in the serum of three of the four patients and were predominantly immunoglobulin G. Few or no antipilus antibodies were present in the urine of infected or control patients. These results suggest that a serological response to the pill of infecting organisms develops after pyelonephritis.

Animals↗

PubMed1971

Renal lysozyme levels in animals developing "sterile pyelonephritis".

The induction of sterile unilateral pyelonephritis in rats with heat-killed Proteus mirabilis cells is described. The lesions were identical to those produced with viable bacteria. Lysozyme levels in both kidneys of rats developing unilateral sterile pyelonephritis underwent biphasic elevations similar to those produced with viable bacteria. In the injected kidney, the first elevation, associated with the trauma of injection, could be produced by injecting sterile saline. The second elevation was associated with the onset of chronicity in the injected kidney. The nonmanipulated, contralateral kidney showed a similar biphasic elevation, of equal duration but of greater magnitude.

Animals↗

PubMed1983

Effect of indomethacin on the incidence of experimental Escherichia coli pyelonephritis.

In the presence of temporary obstruction (20 h), ascending Escherichia coli urinary infection leads to irreversible acute exudative pyelonephritis (AEP) in rats. The purpose of the present study was to investigate the early inflammatory events which take place in response to the presence of bacteria in the kidney parenchyma and lead to the development of AEP. Rats were given indomethacin before and during the obstructive phase of kidney infection and were sacrificed at different times thereafter. Although renal infection (as defined by bacterial counts) was equally frequent (76%) and severe in indomethacin-treated and control rats sacrificed at the end of the obstructive period, it was found that the incidence of AEP (as defined by the inflammatory response of the kidney elicited by bacteria) 2 days after removal of the obstruction was significantly reduced from 74% in controls given water to 48% in indomethacin-treated animals (P = 0.02). Rat kidneys without AEP had bacterial counts of 10(2)/g. Since indomethacin apparently had no direct antibacterial activity against E. coli and no effect on urine osmolalities, it is likely that the reduction in the incidence of AEP and the concomitant eradication of bacteria after removal of the obstruction was due to an effect of indomethacin that is related to the renal response to infection. This was possibly due to decreased inflammation, as indicated by the fact that when pyelonephritis developed in indomethacin-treated rats it was less severe than in controls. These results suggest that if inflammation can be mitigated when bacteria are present in the kidney during obstruction, the bacteria may be cleared spontaneously once the normal urinary flow is restored.

Animals↗

PubMed1994

Enterococcus faecalis aggravates pyelonephritis caused by Pseudomonas aeruginosa in experimental ascending mixed urinary tract infection in mice.

Mixed urinary tract infection was caused by simultaneous inoculation of 10(4) CFU each of Enterococcus faecalis TN2005 and Pseudomonas aeruginosa P9 into the bladders of CBA/J mice. Both organisms proliferated in the kidneys, and viable cell counts of E. faecalis TN2005 reached a peak level of 4.1 x 10(5) CFU per pair of kidneys within the first 24 h, while P. aeruginosa P9 counts increased more slowly. The number of P. aeruginosa P9 cells peaked at 8.3 x 10(6) CFU per pair of kidneys 5 days after infection. Five days after mixed infection, infiltration of neutrophils into the renal pelvis and renal medulla was observed. Immunohistochemical staining revealed the presence of E. faecalis antigen in the renal medulla. P. aeruginosa antigen was detected mainly in the renal pelvis 5 days after infection and in the renal medulla as well as the renal pelvis 14 days after infection. Mixed infection induced pyelonephritis within 5 days after mixed infection, while it was not observed until 14 days after infection with P. aeruginosa P9 alone. P. aeruginosa P9 inoculated together with E. faecalis TN2005 was more resistant to eradication from the kidneys by beta-lactam antibiotics than P. aeruginosa P9 inoculated alone. These results suggest that E. faecalis TN2005 invades the renal medulla first in mixed urinary tract infection and induces histological changes which lead to aggravation of the pyelonephritis caused by P. aeruginosa P9.

Animals↗

PubMed1995

dra-related X adhesins of gestational pyelonephritis-associated Escherichia coli recognize SCR-3 and SCR-4 domains of recombinant decay-accelerating factor.

Bacterial adhesins are important virulence factors that allow colonization of the human urogenital tract by Escherichia coli. Adhesins of the Dr family have been found to be more frequently expressed in strains associated with symptomatic urinary tract infections. Because of the high frequency of symptomatic urinary tract infections during pregnancy, we screened E. coli isolates from 64 gestational pyelonephritis patients for the expression of Dr and X adhesins to address their potential virulence roles in this population. Using PCR and primers for the afaB gene, we detected dra-related operons in 17 isolates (27%). On the basis of the lack of hemagglutination of Dr(a-) erythrocytes containing a point mutation in the decay-accelerating factor (DAF) short consensus repeat-3 (SCR-3) domain, 12 of these strains were categorized as classical Dr adhesins. The hemagglutination of O erythrocytes by Dr+ strains was blocked or reduced by a monoclonal antibody to the DAF SCR-3 domain. The remaining five dra-positive strains agglutinated Dr(a-) erythrocytes. Monoclonal antibody to the DAF SCR-3 domain failed to block O-erythrocyte hemagglutination. Adhesins in these strains did not fulfill criteria for Dr hemagglutinins because of the undefined receptor specificities and were categorized as X. E. coli strains bearing dra-related X adhesins bound to DAF cDNA-transfected Chinese hamster ovary cells. Three of these dra-related X-adhesin-bearing E. coli strains failed to attach to the SCR-3 delta deletion transfectant, which suggested that binding sites were located in the SCR-3 domain but outside the region blocked by the monoclonal anti-SCR-3 immunoglobulin G. The binding sites of the remaining two dra-related X adhesin strains were localized to the SCR-4 domain, as the attachment was shown to be abolished on an SCR-4 delta mutant but unaffected by an SCR-3 delta deletion. The heterogeneity in the binding sites of E. coli DAF (Dr) family adhesins from gestational pyelonephritis isolates may reflect the ability of the adhesins to evolve to recognize alternate peptide epitopes for efficient colonization.

Adhesins, Escherichia coli↗

PubMed1997

Molecular cloning and characterization of Dr-II, a nonfimbrial adhesin-I-like adhesin isolated from gestational pyelonephritis-associated Escherichia coli that binds to decay-accelerating factor.

Bacterial adhesins play an important role in the colonization of the human urogenital tract. Escherichia coli Dr family adhesins have been found to be frequently expressed in strains associated with pyelonephritis in pregnant females. The tissue receptor for known Dr adhesins has been localized to the short consensus repeat-3 (SCR-3) domain of decay accelerating factor (DAF), a complement regulatory protein. In this report, we identified and cloned draE2, a gene encoding a novel 17-kDa DAF-binding adhesin, Dr-II, from a strain of E. coli associated with acute gestational pyelonephritis. Despite the significant sequence diversity between Dr-II and Dr family adhesins, the receptor of Dr-II was found to be the SCR-3 domain of DAF. Sequence analysis of the 186-amino-acid Dr-II open reading frame revealed significant diversity from other members of the Dr adhesin family, including Dr, AFA-I, AFA-III, and F1845, but only an 8-amino-acid difference in sequence from that of the 17-kDa nonfimbrial adhesin NFA-I of unknown receptor specificity. N-terminal peptide sequencing of the purified adhesin confirmed the identity of the open reading frame and indicated cleavage of a 28-amino-acid signal peptide. Antibodies raised against purified Dr-II adhesin exhibited little or no cross-reactivity to Dr adhesin. Characterization of the biological properties demonstrated that like the Dr adhesins, Dr-II was associated with the ability of E. coli to bind to tubular basement membranes and Bowman's capsule and to be internalized into HeLa cells.

Adhesins, Escherichia coli↗

PubMed1978

Occurrence of mycoplasmas in urinary tracts of patients with acute pyelonephritis.

Mycoplasma hominis was isolated from the upper urinary tract in 7 of 80 patients with acute pyelonephritis and from 0 of 60 patients with noninfectious diseases of the urinary tract, a significant difference. In four cases M. hominis was isolated in pure culture, in one it was isolated together with Ureaplasma urealyticum, and in two it was isolated with bacteria. U. urealyticum was isolated from the upper urinary tract of five patients, all with acute pyelonephritis; this was not significantly different from the control group.

Acute Disease↗

PubMed1979

Diagnosis of Mycoplasma hominis pyelonephritis by demonstration of antibodies in urine.

To evaluate the diagnostic significance of the demonstration in urine of antibodies to Mycoplasma hominis, 1,000 samples of urine with more than 5 leukocytes per high-power field were serologically investigated by indirect hemagglutination, using glutaraldehyde-fixed erythrocytes coated with M. hominis antigen. The samples were collected from 702 patients. Antibodies were demonstrated in the urine of nine patients, all of whom had signs of acute attack of pyelonephritis. In seven of these patients, characterized by mild or moderate clinical signs and absence of lower urinary tract symptoms, bacterial causes were not observed, whereas M. hominis organisms were isolated from the upper urinary tract in most cases and from the bladder urine in all cases. In two patients, characterized by severe clinical signs and presence of lower urinary tract symptoms, both M. hominis and bacteria were isolated from the upper urinary tract and ballder urine. The demonstration of antibodies to M. hominis in urine is of high diagnostic value as they were only observed in patients in whom M. hominis infection in the upper urinary tract was evident or likely and only in the presence of clinical signs of acute attacks of pyelonephritis.

Adolescent↗

PubMed2001

Randomised controlled trial of three day versus 10 day intravenous antibiotics in acute pyelonephritis: effect on renal scarring.

BACKGROUND: Acute pyelonephritis often leaves children with permanent renal scarring. AIMS: To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days. METHODS: In a prospective two centre trial, 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy, were randomly assigned to receive intravenous ceftriaxone (50 mg/kg once daily) for 10 or three days, followed by oral cefixime (4 mg/kg twice daily) to complete a 15 day course. After three months, scintigraphy was repeated in order to diagnose renal scars. RESULTS: Renal scarring developed in 33% of the 110 children in the 10 day intravenous group and 36% of the 110 children in the three day group. Children older than 1 year had more renal scarring than infants (42% (54/129) and 24% (22/91), respectively). After adjustment for age, sex, duration of fever before treatment, degree of inflammation, presence of vesicoureteric reflux, and the patients' recruitment centres, there was no significant difference between the two treatments on renal scarring. During follow up, 15 children had recurrence of urinary infection with no significant difference between the two treatment groups. CONCLUSION: In children with acute pyelonephritis, initial intravenous treatment for 10 days, compared with three days, does not significantly reduce the development of renal scarring.

Acute Disease↗